Human-machine interface hardware: The next decade

In order to understand where human-machine interface hardware is headed, it is important to understand where we are today, how we got there, and what our goals for the future are. As computers become more capable, faster, and programs become more sophisticated, it becomes apparent that the interface hardware is the key to an exciting future in computing. How can a user interact and control a seemingly limitless array of parameters effectively? Today, the answer is most often a limitless array of controls. The link between these controls and human sensory motor capabilities does not utilize existing human capabilities to their full extent. Interface hardware for teleoperation and virtual environments is now facing a crossroad in design. Therefore, we as developers need to explore how the combination of interface hardware, human capabilities, and user experience can be blended to get the best performance today and in the future

Statistical Design in Isothermal Aging of Polyimide Resins

Recent developments in research on polyimides for high temperature applications have led to the synthesis of many new polymers. Among the criteria that determines their thermal oxidative stability, isothermal aging is one of the most important. Isothermal aging studies require that many experimental factors are controlled to provide accurate results. In this article we describe a statistical plan that compares the isothermal stability of several polyimide resins, while minimizing the variations inherent in high-temperature aging studies

The Sensitivity and Psychometric Properties of a Brief Computer-Based Cognitive Screening Battery in a Depression Clinic

At present, there is poor accuracy in assessing cognitive and vegetative symptoms in depression using clinician or self-rated measures, suggesting the need for development of standardized tasks to assess these functions. The current study assessed the psychometric properties and diagnostic specificity of a brief neuropsychological screening battery designed to assess core signs of depression; psychomotor retardation, attention and executive functioning difficulties, and impaired emotion perception within an outpatient psychiatry setting. Three hundred eighty-four patients with mood disorders and 77 healthy volunteers participated. A large percentage of patients met diagnostic criteria for Major Depressive Disorder alone (49%) or with another comorbid psychiatric disorder (24%). A brief, 25-min battery of computer-based tests was administered to control participants and patients measuring the constructs of inhibitory control, attention, visual perception, and both executive and visual processing speed. The patient groups performed significantly worse than the control group regardless of diagnosis on visual perception and attention accuracy and processing speed factors. Surprisingly, the anxiety disorder group performed better than several other psychiatric disorder groups in inhibitory control accuracy. Developing valid and reliable measures of cognitive signs in mood disorders creates excellent opportunities for tracking cognitive status prior to initiation of treatment, and allows for reliable retest following treatment

The epidemiology of regional and widespread musculoskeletal pain in rural versus urban settings in those ≥55 years

Objectives: To examine whether the prevalence of regional and chronic widespread pain (CWP) varies with rurality and to determine the characteristics of persons in rural locations in whom pain is found to be in excess. Methods: Participants, aged ≥55 years, from participating general practices in seven different geographical locations in Scotland were sent a postal questionnaire. The 1-month prevalence of 10 regional pain conditions plus CWP was identified using body manikins. Differences in the prevalence of pain with differing rurality were examined using Chi2 test for trend. Thereafter, among the rural population, the relationships between pain and putative risk factors were examined using Poisson regression. Thus, results are described as risk ratios. Results: There was some evidence to suggest that the prevalence of CWP increased with increasing rurality, although the magnitude of this was slight. No large or significant differences were observed with any regional pain conditions. Factors associated with the reporting of CWP included poor general health, feeling downhearted most of the time and selected measures of social contact. Factors independently associated with CWP included female gender (risk ratio: 1.24; 95% confidence interval (CI): 0.997–1.55), poor self-rated health (risk ratio: 3.50; 95% CI: 1.92–6.39) and low mood (risk ratio: 1.54; 95% CI: 1.07–2.20). Also, having fewer than 10 people to turn to in a crisis was associated with a decrease in the risk of CWP – risk ratio: 0.68 (95% CI: 0.50–0.93) and 0.78 (95% CI: 0.60–1.02) for those with 5–10 and <5 people, respectively. Conclusions: This study provides no evidence that the prevalence of regional musculoskeletal pain is increased in rural settings, although there is some evidence of a modest increase in CWP. Risk factors for CWP are similar to those seen in the urban setting, including markers of general health, mental health and also aspects of social contact. It may be, however, that social networks are more difficult to maintain in rural settings, and clinicians should be aware of the negative effect of perceived social isolation on pain in rural areas

C/EBPβ-1 promotes transformation and chemoresistance in Ewing sarcoma cells.

CEBPB copy number gain in Ewing sarcoma was previously shown to be associated with worse clinical outcome compared to tumors with normal CEBPB copy number, although the mechanism was not characterized. We employed gene knockdown and rescue assays to explore the consequences of altered CEBPB gene expression in Ewing sarcoma cell lines. Knockdown of EWS-FLI1 expression led to a decrease in expression of all three C/EBPβ isoforms while re-expression of EWS-FLI1 rescued C/EBPβ expression. Overexpression of C/EBPβ-1, the largest of the three C/EBPβ isoforms, led to a significant increase in colony formation when cells were grown in soft agar compared to empty vector transduced cells. In addition, depletion of C/EBPβ decreased colony formation, and re-expression of either C/EBPβ-1 or C/EBPβ-2 rescued the phenotype. We identified the cancer stem cell marker ALDH1A1 as a target of C/EBPβ in Ewing sarcoma. Furthermore, increased expression of C/EBPβ led to resistance to chemotherapeutic agents. In summary, we have identified CEBPB as an oncogene in Ewing sarcoma. Overexpression of C/EBPβ-1 increases transformation, upregulates expression of the cancer stem cell marker ALDH1A1, and leads to chemoresistance

Structural basis of TRAPPIII‐mediated Rab1 activation

The GTPase Rab1 is a master regulator of the early secretory pathway and is critical for autophagy. Rab1 activation is controlled by its guanine nucleotide exchange factor, the multisubunit TRAPPIII complex. Here, we report the 3.7 Å cryo‐EM structure of the Saccharomyces cerevisiae TRAPPIII complex bound to its substrate Rab1/Ypt1. The structure reveals the binding site for the Rab1/Ypt1 hypervariable domain, leading to a model for how the complex interacts with membranes during the activation reaction. We determined that stable membrane binding by the TRAPPIII complex is required for robust activation of Rab1/Ypt1 in vitro and in vivo, and is mediated by a conserved amphipathic α‐helix within the regulatory Trs85 subunit. Our results show that the Trs85 subunit serves as a membrane anchor, via its amphipathic helix, for the entire TRAPPIII complex. These findings provide a structural understanding of Rab activation on organelle and vesicle membranes

Structural basis of TRAPPIII‐mediated Rab1 activation

The GTPase Rab1 is a master regulator of the early secretory pathway and is critical for autophagy. Rab1 activation is controlled by its guanine nucleotide exchange factor, the multisubunit TRAPPIII complex. Here, we report the 3.7 Å cryo‐EM structure of the Saccharomyces cerevisiae TRAPPIII complex bound to its substrate Rab1/Ypt1. The structure reveals the binding site for the Rab1/Ypt1 hypervariable domain, leading to a model for how the complex interacts with membranes during the activation reaction. We determined that stable membrane binding by the TRAPPIII complex is required for robust activation of Rab1/Ypt1 in vitro and in vivo, and is mediated by a conserved amphipathic α‐helix within the regulatory Trs85 subunit. Our results show that the Trs85 subunit serves as a membrane anchor, via its amphipathic helix, for the entire TRAPPIII complex. These findings provide a structural understanding of Rab activation on organelle and vesicle membranes

An Open Pilot Study of Training Hostile Interpretation Bias to Treat Disruptive Mood Dysregulation Disorder

Objective: Irritability in disruptive mood dysregulation disorder (DMDD) may be associated with a biased tendency to judge ambiguous facial expressions as angry. We conducted three experiments to explore this bias as a treatment target. We tested: 1) whether youth with DMDD express this bias; 2) whether judgment of ambiguous faces can be altered in healthy youth by training; and 3) whether such training in youth with DMDD is associated with reduced irritability and associated changes in brain function. Methods: Participants in all experiments made happy versus angry judgments of faces that varied along a happy to angry continuum. These judgments were used to quantify a “balance point,” the facial expression at which a participant's judgment switches from predominantly happy to predominantly angry. We first compared balance points in youth with DMDD (n = 63) versus healthy youth (n = 26). We then conducted a double-blind, randomized controlled trial of active versus sham balance-point training in 19 healthy youth. Finally, we piloted open, active balance-point training in 14 youth with DMDD, with 10 completing an implicit functional MRI (fMRI) face-emotion processing task. Results: Relative to healthy youth, DMDD youth manifested a shifted balance point, expressed as a tendency to classify ambiguous faces as angry rather than happy. In both healthy and DMDD youth, active training is associated with a shift in balance point toward more happy judgments. In DMDD, evidence suggests that active training may be associated with decreased irritability and changes in activation in the lateral orbitofrontal cortex. Conclusions:These results set the stage for further research on computer-based treatment targeting interpretation bias of angry faces in DMDD. Such treatment may decrease irritability and alter neural responses to subtle expressions of happiness and anger

Bidirectional protein transport between the ER

■ Abstract The endoplasmic reticulum (ER) and the Golgi comprise the first two steps in protein secretion. Vesicular carriers mediate a continuous flux of proteins and lipids between these compartments, reflecting the transport of newly synthesized proteins out of the ER and the retrieval of escaped ER residents and vesicle machinery. Anterograde and retrograde transport is mediated by distinct sets of cytosolic coat proteins, the COPII and COPI coats, respectively, which act on the membrane to capture cargo proteins into nascent vesicles. We review the mechanisms that govern coat recruitment to the membrane, cargo capture into a transport vesicle, and accurate delivery to the target organelle

Soil erosion in a British watershed under climate change as predicted using convection-permitting regional climate projections

Climate change can lead to significant environmental and societal impacts; for example, through increases in the amount and intensity of rainfall with the associated possibility of flooding. Twenty-first-century climate change simulations for Great Britain reveal an increase in heavy precipitation that may lead to widespread soil loss by rising the likelihood of surface runoff. Here, hourly high-resolution rainfall projections from a 1.5 km (‘convection-permitting’) regional climate model are used to simulate the soil erosion response for two periods of the century (1996–2009 and a 13-year future period at ~2100) in the “Rother” catchment, West Sussex, England. Modeling soil erosion with EROSION 3D, we found a general increase in sediment production (off-site erosion) for the end of the century of about 43.2%, with a catchment-average increase from 0.176 to 0.252 t ha−1 y−1 and large differences between areas with diverse land use. These results highlight the effectiveness of using high-resolution rainfall projections to better account for spatial variability in the assessment of long-term soil erosion than other current methods